Alcoholism heritability has been established in both men and women, but, as for other complex psychiatric diseases, it has proved difficult to map genes. We have identified an intermediate marker for alcoholism vulnerability, the low voltage alpha (LVA) EEG, a normal, traitlike heritable variant of the resting EEG, present in 4-11% of the population, in which the alpha rhythm is virtually absent. We now have a complete data set, including EEG and ERP phenotypes, blind-rated DSM-III-R diagnoses, psychometric tests and DNA on 247 individuals from Bethesda, MD. We have shown that in these subjects, LVA is associated with alcoholism, particularly when accompanied by anxiety disorders (Enoch et al 1995,1999). Moreover, we found that LVA individuals had reduced amplitude P300 ERPs, further strengthening our argument for the association of LVA with alcoholism vulnerability. As expected, P300 amplitude was reduced in alcoholics, however, it was lowest in alcoholics with comorbid anxiety disorders and highest in individuals with anxiety disorders alone (Enoch et al 2001). In order to obtain sufficient power to map genes for alcoholism we have also studied a Plains American Indian tribe which has a high prevalence of alcoholism.We now have EEGs and ERPs on 374 tribal members from large pedigrees and have almost completed the data set of blind-rated DSM-III-R psychiatric diagnoses and DNA from these individuals. Preliminary studies confirm the relationship of LVA with alcoholism and anxiety disorders. We will soon be in a position to commence analyses for mapping genes for alcoholism. We have started candidate gene analysis and have found that in both Bethesda and Plains Indian women, the low activity Met allele (and particularly the Met/Met homozygote) of the catechol-O-methyltransferase (COMT) functional polymorphism Val158Met is associated both with LVA and harm avoidance, a dimensional measure of anxiety (Enoch et al submitted). Formerly titled "Genetic studies of the electroencephalogram and event-related potentials."